Angiotensin-converting enzyme inhibitors reliably reduce hematocrits in renal transplant patients with erythrocytosis, through an undefined mechanism, independent of changes in circulating erythropoietin. We treated 18 patients with posttransplant erythrocytosis with losartan, which antagonizes action of angiotensin II by binding to its receptor. Eleven patients whose hematocrits increased by at least 4 percentage points after withdrawal of enalapril (from 45.4 +/- 52.0 +/- 3.4 by 8-12 weeks after withdrawal), and 7 previously untreated patients with hematocrit 52.9 +/- 2.0 were studied. Dosage of losartan was 25 or 50 mg per day. We measured hematocrit, serum potassium and creatinine levels, and mean arterial blood pressure at 4-week intervals. Hematocrit decreased significantly after 8 weeks of losartan treatment. In 15 patients on therapy for 12 weeks the hematocrit has further decreased to 48.9 +/- 4.8 (p=0.007 compared to their pretreatment baseline). At last follow-up, the hematocrit has decreased by at least 4 points in 15 of 18 (83%) patients. Assays for measurement of plasma erythropoietin, angiotensin II, and peripheral renin activity have not yet been completed. Therapy was well tolerated. Although the serum potassium level increased and mean arterial blood pressure decreased significantly, no patient withdrew due to severe hyperkalemia or symptomatic hypotension. Thus, losartan effectively reduced hematocrit in patients with posttransplant erythrocytosis. This effect implies that angiotensin II stimulates erythropoiesis in some renal transplant patients, directly or indirectly.